[177Lu]Lu-PSMA-617 Plus Enzalutamide Boosts Survival, Quality of Life for Poor-Risk Metastatic Castration-Resistant Prostate Cancer
According to results from the phase 2 ENZA-p trial, the addition of [177Lu]Lu-PSMA-617 (LuPSMA) to enzalutamide improved the overall survival and several quality-of-life measures among patients with poor-risk, metastatic castration-resistant prostate cancer (mCRPC).
This open-label, controlled phase 2 trial enrolled patients with poor-risk, mCRPC who had not received chemotherapy or an androgen receptor pathway inhibitor for mCRPC, had 68Ga-PSMA PET-avid disease, and at least 2 risk factors for early disease progression on enzalutamide alone. Patients were randomized to receive 160 mg enzalutamide daily either alone or in combination with 7.5 GBq LuPSMA for either 2 or 4 doses. Health-related quality of life scores (ranging from 0 to 100) were evaluated via EORTC core quality-of-life questionnaire every 6 weeks until radiological progression. At an earlier reported interim analysis with a median follow-up of 20 months, there was an improvement of PSA–progression-free survival and depth of PSA-response in the LuPSMA arm. This analysis reports on overall survival (OS) and health-related quality of life.
With a median follow-up of 34 months, the OS was longer in the LuPSMA arm (34 months) than the enzalutamide alone arm (26 months; hazard ratio [HR], 0.55; P = .005). From the enzalutamide alone arm, 38% of patients received LuPSMA off trial. There were 95% of patients who were rated for health-related quality of life. At 12-months, deterioration-free survival rates favored the LuPSMA arm for both overall health and quality of life (P < .001) and physical function (P < .001). Mean scores for pain until progression and for fatigue until progression also both favored the LuPSMA arm. The frequency of self-rated xerostomia was lower in the enzalutamide alone arm.
Dr Emmett and coauthors concluded, “The addition of LuPSMA to enzalutamide in poor-risk mCRPC improved overall survival, scores for pain and fatigue, and deterioration-free survival for both physical function and for OHQL.”
Source:
Emmett L, Subramaniam S, Crumbaker M, et al. Overall survival and quality of life with [177Lu] Lu-PSMA-617 plus enzalutamide versus enzalutamide alone in poor-risk, metastatic castration-resistant prostate cancer in ENZA-p (ANZUP 1901). Presented at 2025 ASCO Genitourinary Cancers Symposium. February 13-15, 2025; San Francisco, CA. Abstract 17
